Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously found a relative sparing of somatostatin and neuropeptide Y neurons 1 week after producing striatal lesions with NMDA receptor agonists. These results are similar to postmortem findings in Huntington's disease (HD), though in this illness there are two- to threefold increases in striatal somatostatin and neuropeptide Y concentrations, which may be due to striatal atrophy. In the present study, we examined the effects of striatal excitotoxin lesions at 6 months and 1 yr, because these lesions exhibit striatal shrinkage and atrophy similar to that occurring in HD striatum. At 6 months and 1 yr, lesions with the NMDA receptor agonist quinolinic acid (QA) resulted in significant increases (up to twofold) in concentrations of somatostatin and neuropeptide Y immunoreactivity, while concentrations of GABA, substance P immunoreactivity, and ChAT activity were significantly reduced. In contrast, somatostatin and neuropeptide Y concentrations did not increase 6 months after kainic acid (KA) or alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) lesions. At both 6 months and 1 yr, QA lesions showed striking sparing of NADPH-diaphorase neurons as compared with both AMPA and KA lesions, neither of which showed preferential sparing of these neurons. Long-term QA lesions also resulted in significant increases in concentrations of both 5-HT and 5-hydroxyindoleacetic acid (HIAA), similar to findings in HD. Chronic QA lesions therefore closely resemble the neurochemical features of HD, because they result in increases in somatostatin and neuropeptide Y and in 5-HT and HIAA. These findings strengthen the possibility that an NMDA receptor-mediated excitotoxic process could play a role in the pathogenesis of HD.
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PMID:Chronic quinolinic acid lesions in rats closely resemble Huntington's disease. 171 Jun 57

Antisera raised against the fixation products of L-glutamate and L-aspartate were used, singly or in combination, to study the ultrastructural localization of the amino acids in the rat dorsal horn, with post-embedding immunogold techniques. Immunostaining for each of the amino acids was also combined with immunolocalization of GABA, an important inhibitory neurotransmitter in the spinal cord, or synaptophysin, a synaptic vesicle glycoprotein. In addition, we examined the localization of glutamate immunoreactivity in relation to that of calcitonin-gene related peptide and substance P, two neuropeptides present in high concentrations in the dorsal horn. Glutamate- and aspartate-immunoreactive neuronal cell bodies, dendrites, axons and terminals were apparent in the first three laminae of the dorsal horn. In somatic and dendritic profiles, the immunolabel was present over the general cytoplasm and mitochondria; in the terminals, it was found over small, agranular vesicles, mitochondria and, at times, synaptic densities. Quantitative estimation indicated that the colloidal gold density in the glutamate-immunoreactive terminals was five-fold more than in any other neuronal profile. Both glutamate- and aspartate-immunopositive terminals made asymmetric synaptic contacts onto unlabelled dendrites; glutamate-positive terminals often formed the core of type I and II glomeruli. After double labelling of the same sections, glutamate and aspartate immunoreactivities consistently occurred in different axonal and terminal profiles. In these preparations, it was clearly seen that glutamate-immunoreactive terminals were far more numerous than (more than 10-fold) those immunoreactive for aspartate. Double labelling for glutamate or aspartate and GABA also revealed distinct staining of different terminals. Simultaneous immunolocalization of each of the amino acids and synaptophysin showed the amino acid and glycoprotein immunoreactivities co-localized in small, agranular vesicles in immunoreactive terminals. Finally, triple labelling of the same sections for glutamate, calcitonin gene-related peptide and substance P revealed that glutamate was often co-localized with either of the two neuropeptides in the same axonal boutons; terminals that showed simultaneous labelling for glutamate, calcitonin gene-related peptide and substance P were also noted. In all cases, the glutamate immunoreactivity was restricted to small, clear vesicles whereas the neuropeptide immunoreactivities were present in larger, dense-cored vesicles. Our observations demonstrate that there is an abundant glutamate immunoreactivity in the superficial layers of the rat dorsal horn, localized in neuronal profiles distinct from those containing aspartate or GABA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ultrastructural visualization of glutamate and aspartate immunoreactivities in the rat dorsal horn, with special reference to the co-localization of glutamate, substance P and calcitonin-gene related peptide. 171 Nov 77

Adult monkey sensorimotor cortex consists of several structurally and functionally distinct areas. The developmental sequence through which the characteristic architectonic features and the borders of these areas become resolved was examined in a series of fetal, postnatal and adult monkeys by using Nissl staining, cytochrome oxidase and acetylcholinesterase histochemistry, and immunocytochemistry for GABA and the neuropeptides somatostatin, neuropeptide Y, substance P and cholecystokinin. At the youngest fetal age examined (E110), the pre- and postcentral gyri possess six clearly delineated cellular layers; populations of GABA- and neuropeptide-immunoreactive cells can be identified, but their somatic sensory cortex at E110 lacks areal cytoarchitectonic parcellation. Despite the apparent homogeneity in the cytoarchitecture of the somatic sensory cortex, incipient areal borders are revealed by staining for cytochrome oxidase and acetylcholinesterase activity, and by staining immunocytochemically for several neuropeptides. The motor cortex at E110 differs from that in adults by the presence of a prominent layer IV; a clear cytoarchitectonic border between areas 3a and 4 is detectable at E110, which is also revealed by chemoarchitectonic markers. With increasing age, the characteristic architectonic features gradually emerge and areal cytoarchitectonic borders appear, becoming adult-like by early postnatal ages. The gradual changes in cytoarchitecture are paralleled by redistributions of GABA- and neuropeptide-immunoreactive cells and fiber plexuses. The data demonstrate that the progressive refinement in cytoarchitectonic features and in the distributions of neurotransmitter- and peptide-containing cells occurs primarily during the latter third of gestation. The major changes are temporally coincident with the ingrowth of afferent axonal systems, suggesting that the establishment of connectivity may be capable of modulating finer details of structural or molecular phenotype, particularly intra-areal cytoarchitectonic features and neurotransmitter or peptide expression.
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PMID:The emergence of architectonic field structure and areal borders in developing monkey sensorimotor cortex. 171 47

In the present studies the effects of kainic acid (KA)- or quinolinic acid (QA)-induced striatal lesions were compared in different behavioral tests in rats. Both KA- and QA-lesioned animals had ipsilateral barrel-rotation (BR). The KA-lesioned rats, however, had contralateral, while the QA-lesioned rats had both ipsi- and contralateral turning activity. The KA-lesioned animals showed increased open-field activity as well as increased percentage of entries, and time spent in the open arms of Montgomery's conflict test. Learning of an active avoidance response was strongly inhibited by both striatal QA- or KA-induced striatal lesions. The QA-lesioned animals showed less pronounced behavioral changes than KA-lesioned animals in most of the tests, and had a smaller loss of body weight. There was no significant difference in the extent of the KA- and QA-induced substance P (SP) and GABA depletions in striatum, however, the depletions with QA lesions were slightly greater. These findings show that KA-induced striatal lesions produce more pronounced behavioral effects than QA lesions of similar size. It is possible that the differential effects of KA versus QA on striatal interneurons may result in its more marked behavioral effects.
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PMID:Comparative behavioral and neurochemical studies with striatal kainic acid- or quinolinic acid-lesioned rats. 171 69

Isolated spinal cords of newborn rats were perfused with artificial cerebrospinal fluid and the effects of substance P and its analogs on the release of endogenous GABA were examined. Application of substance P evoked a dose-dependent release of GABA from spinal cords. The threshold concentration of substance P for induction of a significant increase in the GABA release was 3 microM. The substance P-evoked GABA release was neither blocked by removal of Ca2+ from perfusion medium nor by tetrodotoxin. In contrast, the GABA release evoked by high K+ (90 mM) was abolished in Ca(2+)-free medium, and the GABA release evoked by veratridine (5 microM) was suppressed by tetrodotoxin (1 microM). A GABA uptake inhibitor, cis-4-hydroxynipecotic acid, markedly augmented the GABA release induced by high K+, but not that induced by substance P or veratridine. These results suggest the possibility that a carrier-mediated mechanism might be involved in the GABA release induced by substance P, as well as by veratridine, in the newborn rat spinal cord. Two N-terminal fragments of substance P, substance P free acid and substance P1-10 amide, as well as [D-Arg1,D-Trp7,9,Leu11]substance P (spantide), evoked an increase in the GABA release, whereas substance P1-6, and a C-terminal fragment, substance P5-11 were inactive. Somatostatin and compound 48/80 also evoked a GABA release, which was independent of external Ca2+ and resistant to tetrodotoxin. [D-Pro4,D-Trp7,9,10]substance P4-11 (10-15 microM) inhibited the GABA release evoked by substance P, somatostatin and compound 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substance P-evoked release of GABA from isolated spinal cord of the newborn rat. 172 88

Tardive dyskinesia has been connected with regional reductions of GABA functions in the basal ganglia. In view of the possibility that peptides are involved in neuroleptic-induced dyskinesias substance P and dynorphin A levels were measured in the basal ganglia of the Cebus apella model for tardive dyskinesia. In addition, regional glutamate decarboxylase activities, dopamine, homovanillic acid and dihydroxyphenylacetic acid levels were monitored. A significant dyskinesia-related decrease in glutamate decarboxylase activity was found in the subthalamic nucleus, the medial segment of globus pallidus and the rostral part of substantia nigra in accordance with earlier findings. Cebus monkeys with an intact GABA system (neuroleptic-treated controls without dyskinesia) showed increased levels of substance P and homovanillic acid in the caudate nucleus. The changes were confined to the caudal part of the body of the caudate and the nucleus accumbens. On the other hand, the dyskinetic monkeys, with a defective GABA system, did not demonstrate a similar substance P rise in the caudate or nucleus accumbens, but showed a depression of homovanillic acid levels in the caudal part of the body of the caudate nucleus. Dynorphin A, dopamine and dihydroxyphenylacetic acid showed no dyskinesia-related changes. In conclusion, the difference in glutamate decarboxylase activity between animals developing dyskinetic symptoms vs those who did not, was reflected by regional changes in substance P and homovanillic acid levels.
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PMID:Neuropeptide changes in a primate model (Cebus apella) for tardive dyskinesia. 172 15

The modulation of Ca2+ currents by neurotransmitters was studied in freshly dissociated rat spinal cord neurons, using the whole-cell patch-clamp technique. GABA, baclofen, adenosine, ATP, serotonin, norepinephrine, somatostatin, and dynorphin A inhibited the current through Ca2+ channels in a substantial fraction of cells, while substance P, vasoactive intestinal polypeptide, [D-ala2,d-leu5]-enkephalin, cholecystokinin-8 (sulfated), calcitonin gene-related peptide, angiotensin II, neurotensin, vasopressin, and thyrotropin-releasing hormone had no effect. In the case of baclofen, the inhibition is mediated, at least in part, by a GTP-binding protein. Suppression of Ca2+ current by neurotransmitters may represent a mechanism of presynaptic inhibition in the spinal cord.
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PMID:Neurotransmitter modulation of calcium current in rat spinal cord neurons. 196 36

The purpose of this study was to determine the nature of the neurochemical signals which impinge on the mesencephalic locomotor region (MLR) to produce locomotion in the rat. Injections of GABA antagonists into NADPH diaphorase-positive regions (PPN) were found to induce locomotion for short episodes (5-30 sec) which were repeated for several minutes (1-40 min). Such activity was blocked by injections of GABA and the GABA agonist, muscimol. Locomotion was induced by injection of substance P (SP), which also produced short, repeated episodes of locomotion. The more potent excitatory amino acid agonist, n-methyl-d-aspartic acid (NMDA), however, did produce dose-dependent, long-lasting (20 sec-5 min) locomotor episodes which were repeated over prolonged periods at the higher concentrations used (2-24 min). Additional injections of NMDA could drive stepping from a walk to a trot to a gallop. The effects of NMDA were blocked by injections of the excitatory amino acid antagonist, aminophosphonovalerionic acid (APV) (1-10 mM). Preliminary evidence suggests that carbachol (10-50 mM), a cholinergic agonist, inhibits NMDA-induced increases in muscle tone and episodes of stepping. The effect of carbachol was blocked by the cholinergic antagonist, atropine.
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PMID:Posterior midbrain-induced locomotion. 197 Sep 47

This study utilized the technique of in situ hybridization histochemistry to identify cells expressing neurotransmitter mRNAs in embryonic striatal tissue grafts implanted into the ibotenic acid-lesioned rat neostriatum. Synthetic 32P- or 35S-labelled oligodeoxyribonucleotide probes specific for prosomatostatin, proneuropeptide Y. proenkephalin, prodynorphin and preprotachykinin mRNAs and a 32P-labelled cRNA probe specific for glutamate decarboxylase mRNA were used to study the regional and cellular changes in these mRNA levels in the normal, lesioned and grafted neostriatum. The levels of neuropeptide Y mRNA and somatostatin mRNA were substantially increased in the striatal grafts compared with the intact control striata. The levels of glutamate decarboxylase mRNA in the grafts also appeared to be slightly elevated over those in the control striata. However, the levels of proenkephalin mRNA, prodynorphin mRNA and preprotachykinin mRNA were significantly lower in the grafts. The increased levels of neuropeptide Y mRNA and somatostatin mRNA in the grafts were due both to an increase in the number of labelled cells and to an increase in the cellular levels of each neuropeptide mRNA. In contrast, the cellular levels of proenkephalin mRNA, prodynorphin mRNA and preprotachykinin mRNA in the grafts were comparable, or elevated relative, to those in the intact striata but the density of cells expressing each of these mRNAs was reduced. Since neuropeptide Y and somatostatin are known to be present in medium to large aspiny striatal neurons (interneurons) and enkephalin, dynorphin and tachykinin peptides and GABA are localized in medium spiny striatal projection neurons, the above findings would indicate that there is a divergence in the levels of activity between these two neuronal populations in the striatal grafts. Our data suggest that the levels of gene expression and hence the functional neurotransmitter-synthesizing and releasing activity in the grafted neuron are different from those in the normal mature striatum.
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PMID:Gene expression in striatal grafts--I. Cellular localization of neurotransmitter mRNAs. 197 68

Sites of action of centrally active muscle relaxant drugs are not well defined. Clinical experience with such drugs suggests that the spinal cord may be one of the important regions from which pathologically increased muscle tone may be relieved. Supraspinal centers that may also be involved in the expression of muscle relaxant action have not yet been defined. We report here that microinjections of therapeutically relevant muscle relaxants into the midbrain tegmentum of genetically spastic rats decrease muscle tone. The substantia nigra is the region from which midazolam, baclofen, and tizanidine (drugs used clinically in the treatment of spasticity), or gamma-vinyl-GABA, (-)-2-amino-7-phosphonoheptanoate, and [D-pro2-D-phe7-D-trp9]-substance P (experimental drugs active in animal models of spasticity), reduce muscle tone in genetically spastic rats and Hoffmann reflexes in normal rats. The effects of muscle relaxant drugs are topographically restricted to the substantia nigra pars reticulata and are receptor specific. These observations disclose a previously unknown function of the substantia nigra in mediating muscle relaxation.
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PMID:Substantia nigra: a site of action of muscle relaxant drugs. 197 34


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